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Analytical Method Validation — ICH Q2(R1) Protocol

1. Validation Parameters and Acceptance Criteria

Parameter Definition Procedure Acceptance Criteria
Specificity Ability to measure analyte without interference from impurities Inject blank, placebo, sample. Check peak purity with DAD spectra Resolution ≥2.0 between target peptide and nearest peak; peak purity angle < purity threshold
Linearity Proportional relationship between concentration and detector response 5 concentration levels (50 – 150% of target), n=3 per level Correlation coefficient R² ≥0.999
Accuracy Closeness of measured value to true value Spike known amount of reference standard at 80, 100, 120% of target Recovery 98.0 – 102.0%
Repeatability Precision under same conditions (same day, analyst, instrument) 6 replicate injections of same sample Area RSD ≤1.0%; Retention time RSD ≤0.5%
Intermediate Precision Precision under different conditions Different analyst, different day, n=6 each RSD ≤2.0% across all results
LOD Limit of detection S/N measurement at low concentration S/N ≥3:1
LOQ Limit of quantification S/N measurement at low concentration; n=6 injection precision S/N ≥10:1; RSD ≤20%
Robustness Resistance to deliberate parameter changes Vary flow (±0.1 mL/min), column temp (±2 °C), pH (±0.1), wavelength (±2 nm) %Change from original ≤2.0%

2. Revalidation Triggers

  • Change in synthesis route for a given peptide
  • Change in column chemistry or dimensions
  • Change in mobile phase composition by >10%
  • Change in detection wavelength
  • Change in sample preparation procedure
  • Annual review (if no changes, confirm method remains valid)